"This was a robust greater than 50% reduction, suggesting probiotic efficacy," she said at the annual Digestive Disease Week here.

The largest of the newer trials, PLACIDE, included 1,493 patients given probiotics and 1,488 receiving placebo. In that study, the incidence of C. difficile diarrhea was 0.8% in the probiotics group and 1.2% in the placebo group (RR 0.71, 95% CI 0.34-1.47, P=0.34). The authors commented that they found "no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention."

Shen cautioned that the data as a whole in the meta-analysis do support the use of probiotics. She explained that the incidence of C. difficile infection in the PLACIDE study was very low, and the study had been powered for an estimated 4% incidence in the control group. "That suggests that it was underpowered," she told MedPage Today.

The timing of the probiotic administration was significant, she noted. When the probiotic was given within 2 days of the first antibiotic dose, the relative risk was 0.32 (95% CI 0.21-0.47), but if it wasn't given until 2 days or more after the first dose, the risk increased (RR 0.70, 95% CI 0.40-1.23), she said.

"C. diff is a leading reported healthcare-associated infection. It's a billion dollar problem that's associated with significant morbidity and mortality, and prevention among patients at high risk is imperative," she said.

A systematic Cochrane review published in 2013 of inpatient and outpatient adults and children showed a relative risk of 0.36 (95% CI 0.26-0.51), which suggested probiotic efficacy.

"Despite these findings, probiotics are not recommended in our professional guidelines for the prevention of C. diff infection in hospitalized adults receiving antibiotics. Neither the American College of Gastroenterology nor the Society for Healthcare Epidemiology of America recommends probiotic use," she said.

In 2015, however, a modified Delphi panel unanimously recommended the use of Lactobacillus acidophilus and L. casei for prevention in patients receiving antibiotics.

"So given these conflicting recommendations and the newer trials published since 2012, we sought to reevaluate this topic with a new systematic review and meta-analysis," Shen said.

She and her colleagues therefore conducted a literature search, initially identifying more than 1,600 citations, of which 19 met their inclusion criteria.

Patients had to be older than 18, hospitalized, and taking antibiotics. Exclusion criteria in the studies were recent diarrhea, immunocompromised state, antibiotic use within the previous 30 days, recent C. difficile infection, and inflammatory bowel disease. The primary outcome was the efficacy of probiotics for C. difficile infection.

Among 3,665 patients taking probiotics, the incidence of C. difficile infection was 1.5%, compared with a rate of 3.5% among 3,277 patients in the control group.

This represented an absolute risk reduction of 2%, she said.

Aside from the timing of probiotic administration, other prespecified subgroup analyses such as potential trial bias, probiotic species, probiotic formulation, and probiotic dose did not change the magnitude of effect. In addition, a funnel plot did not demonstrate evidence of publication bias.

Adverse events in the studies included cramping, nausea, and fever, and occurred no more often in the probiotic group than in the placebo group (RR 0.97). There were no cases of probiotic sepsis.

Limitations of the study included patient loss to follow-up in some studies, though this was equally distributed between the probiotic and control groups, and incomplete C. difficile testing.

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